Interrupting reperfusion reduces neuronal cell death after cerebral ischemia in rats by preventing apoptosis

In this paper we tested the hypothesis that interrupting reperfusion (ischemic postconditioning) reduces the neuron death after transient global cerebral ischemia/reperfusion. Ten min transient cerebral ischemia was induced by four‐vessel occlusion in male Sprague‐Dawley rats. The animals underwent postconditioning consisting of 3 cycles of 15s/15s, 30s/30s or 60s/15s reperfusion/occlusion, respectively, which were applied after the start of reperfusion. Cytosolic expression of cytochrome c and caspase‐3 was evaluated by immunohistochemistry. Ten min ischemia and 7 days reperfusion destroyed approximately 79% of CA1 neurons and 58% parietal cortex neurons, respectively. Three cycles of 30s/30s reperfusion/ischemia postconditioning decreased the neuron loss to 7% in CA1, and 10% in cortex. Another two postconditioning protocols failed to rescue the CA1 neuron death, but decreased the loss of cortex neurons. The expression of cytochrome c at 5h and 12h and caspase‐3 at 12h increased significantly after reperfusion, which was prevented by three cycles of 30s/30s reperfusion/ischemia postconditioning. Our data provide the evidence that appropriate interrupting reperfusion is neuroprotective against global cerebral ischemia/reperfusion injury, and this protective effect is through preventing the activation of caspase and then neuronal apoptosis.